title: Cerebrospinal fluid cytology in patients with cancer: minimizing false-negative results.
abstract: BACKGROUND
  Detection of malignant cells on cytologic examination of the cerebrospinal fluid (CSF) is the diagnostic gold standard for leptomeningeal carcinomatosis. The absence of cells is a primary endpoint for most therapeutic trials. Unfortunately, false-negative results are common. Practical strategies are necessary to remedy this problem.
  
  
  METHODS
  Four physician-dependent variables (CSF sample volume, site of CSF sampling, processing time, and frequency of CSF sampling) were identified, and their contributions to the false-negative rate of CSF cytology were evaluated prospectively in 39 patients with leptomeningeal carcinomatosis. Retrospective data were analyzed to estimate the importance of these variables in daily practice.
  
  
  RESULTS
  False-negative CSF cytology results correlated with small CSF volume (P < 0.001), delayed processing (P < 0.001), not obtaining CSF from a site of symptomatic or radiographically demonstrated disease (P = 0.02), and sampling fewer than two times (P < 0.001). In 1 year, 97% of CSF specimens at the study institution were of inadequate volume; >25% were processed too slowly.
  
  
  CONCLUSIONS
  False-negative CSF cytology results are common, but can be minimized by: 1) withdrawing at least 10.5 mL of CSF for cytologic analysis; 2) processing the CSF specimen immediately; 3) obtaining CSF from a site of known leptomeningeal disease; and 4) repeating this procedure once if the initial cytology is negative.
authors.affiliation: Department of Medicine, Brown University School of Medicine, Providence, Rhode Island, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Glantz
authors.forename: B F
authors.initials: BF
authors.lastname: Cole
authors.forename: L K
authors.initials: LK
authors.lastname: Glantz
authors.forename: J
authors.initials: J
authors.lastname: Cobb
authors.forename: P
authors.initials: P
authors.lastname: Mills
authors.forename: A
authors.initials: A
authors.lastname: Lekos
authors.forename: B C
authors.initials: BC
authors.lastname: Walters
authors.forename: L D
authors.initials: LD
authors.lastname: Recht
mesh_terms: D002555:Cerebrospinal Fluid / Q000166:cytology*; D003581:Cytodiagnosis / Q000379:methods; D005188:False Negative Reactions; D006801:Humans; D008577:Meningeal Neoplasms / Q000473:pathology* / Q000556:secondary; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D013048:Specimen Handling / Q000379:methods; D013129:Spinal Puncture